Chloracetic acid ester of diphenyl ethanols



Patented Aug. 18, 1953 UNITED STATES PATENT OFFICE CHLORACETIC ACID ESTER F DIP-HENYL ETHANOLS Merrill E. Specter, Syracuse, N. Y., assignor to Bristol Laboratories, Syracuse, N. Y., a corporation of New York No Drawing. Application February 28, 1948, Serial No. 12,141

401mm. (01. no -247.2)

, 4 R1 wherein R1 represents an aliphatic hydrocarbon 1 radical (e. g.,.methyl, ethyl, propyl, isopropyl,

allyl, butyl, secondary butyl, isobutyl, butenyl, amyl, methallyl, tertiary-butyl, crotyl, ethallyl, heptyl, isoheptyl, octyl, decyl, isoamyl, hexyl, etc.); R2 represents hydrogen, a lower aliphatic hydrocarbon radical, and radicals having the following structure: 0

where X stands for an aliphatic hydrocarbon cyclohexyl, cyclopentyl, cyclooctyl, etc.) heterocyclic (e. g. a, p, and 'y, pyridyl, a, B and pyrimidyl and a, [3, thienyl, and their homologues, as well as those groups with one or more of their hydrogen atoms substituted by a halogen, more particularly chlorine, bromine, fluorine or iodme. Specific examples of halogen-substituted hydrocarbon radicals are chlorophenyl, dichlorophenyl, chlorocyclohexyl, etc.; R5 is a straight or branched chain alkylene residue containing 1 to 6 carbon atoms; Re and R7 may be hydrogen, an alkyl group (saturated or unsaturated) containing 1 to 6 carbon atoms, and

' 2 Y representing the atoms necessary to complete a heterocyclic ring system (e. g., morpholinyl, piperidyl, pyrrolidyl, etc.) and homologues thereof. This invention also includes all of the isomers of the above compounds.

The acid addition salts of these compounds are also included within the present invention. Some examples of the acid addition salts of the base with inorganic or organic acids which may be prepared by the methods hereinafter described are the hydrochloride, hydrobromide, hydroiodide, sulfate, phosphate, maleate, acetate,

citrate, oxalate, succinate, benzoate, tartrate,

phthalateand the like.

The new compounds are useful for therapeutic applications, many possessing analgetic and antispasmodic activity. These compounds are also useful as intermediates in the preparation of other organic-compounds.

The basically substituted carbinols may be prepared by reducing the corresponding ketones, and the esters obtained by the acylation of the carbinolsl r The present invention also includes compounds which serve as intermediates in the production of the above compounds and to methods for the preparation of the same.

The following examples will serve to illustrate the invention without limiting it thereto, all parts being by weight unless otherwise indicated.

Example 1 The preparation of 2-dimethylamino-4,4-diphenyI-S-heptanol as the free base having the following formula:

H d CH3 The solution was filtered, made basic and extracted with ether. The ether extracts were dried over potassium carbonate and then concentrated. Last traces of ether were removed under reduced pressure. The oil slowly crystallized on V scratching and cooling. 1 The material was then dissolved in boiling Skellysolve C and cooled.

Large (half centimeter) crystals slowly sep- Example 2 .3

The preparation of 2=dimethylamino.=4;4 -diphenyl-5-heptanol hydrochloride having the following formula:

Ten grams (0.03 mole) of amidonehyrdrochloride was dissolved in 100 ml. 'of- 'distilleds water. The solution-was placed in a reduction bottle and 0.5 grams} of Adams platinum oxide cataiystintroduced The com'p ound was then hydrogenated at-room temperature (22 C.) using a Burgess-Parrapparatus with an initial hydrogen pressure of- 55 po unds. In two hours a pres- I sure dropwasobse'rved which indicated absorption er hydrogen. corresponding to that theoretically;required fior reduction of" the carbonyl group} The; reduction was stopped, the catalyst filtered off and -tl1'e 1iltrate concentrated to a volume t; 101:0 15ml oncooling, crystals separ'ated which were-purified through a second re- 1 crystallization f;rom;wa'ter followed by recrystallization from isop'ropanol. 'lhe resulting white crys a ine P wd me tediat Calculated for CmHasNOl-ICI:

' Calculated Found l C 72.47 722 H. 8.68 8. 56 N. V 4. O3 3. 99

ifiEzcampZe 3 The" "preparation"' or 2-"dimethylamino 4,4-diphenyl 5 hptanol'by'ftln use of lithium-aluminum hydride having 'tliefoirnula:

- A solution. of 1-2;.gm.' (0.039, mole) of amido-ne v- 'base in 300ml. dry ether-was added dropwise to a solution of 1.4 gm. (0.04 mole) of lithium aluminum hydride in 250 m1. of dry ether. Some exothermic reaction was'noted and the mixture refluxed gently. After the addition, the mixture was refluxed for 18 hours and was then cooled inan ice-"salt bath.""Small pieces of ice were added over a 30 minute perioduntil no reaction-was evident with liberation oi hydrogen. The mixture was: then poured into a beaker containing 200 ml. of: 20% sodium hydroxide. After stirring'well thegmixture was transferred to a separatory funneland the layersseparated. The

Y ether layer was dried over potassium carbonate while the'waterlayer wasextraoted with 800 ml.

' of ether three' portions. The combined 'dried "ether solutions wefeboncentrated and the resid- "'ual'oil crystallized at once. The 'c'r'ystals' were dissolved in hot Skellysolve C and cooled. The crystals whichseparate'melted at 96-98% A see- 0nd recrystalliz'atiomirom skellysolve O-gave a CH: v:; 7

product which melted at 101102 and also melted undepressed at this temperature with an authentic sample of 2-dimethylamino-4,4-dipheny1- 5-heptanol prepared by catalytic reduction.

Example 4 The preparation .of 2-dimethylamino-4,4-diphenyl-5ea'cetoxyheptane hydrochloride having the formula:

A solutionof ,2 gm. (0.06 mole) of 2-dimethyl- "amino lfl diphehyl-S-heptanol in 100 mil. of dry """ether was treated with 1 m1. of acetyl chloride.

:Theiinixture was cooled in an ice bath and was protected from moisture with a calcium chloride drying. tube. Ihe, white. precipitate .whichslow- 1y separated was recrystallized from. ethyl .ace-

- tate. --'-Ihe precipitate melted 1 at 208"2101' after somesintering atff200l A second recrystallization from: :ethyl. acetate gave crystalsnielting sharply at 213 214L LYield ,1. gm.

7 Calculated for CHiNOi HC1:

3 0 Calculated Found Example 5 -The preparation? of. z-dimethylaminoei irdiphenyl-5ebenzoyloxyheptane":hydrochloride having: the formula:

':5. 4) Iu'JLOH .-.CH CH;+"i- CHz CH N 1 1201 0 H3 visas ..==o1 1e gr m. or the. arbinol "(0.032 mole). in 100 ml. of dryetherwastreated with ligm. of benzoyl chloride (excessh -On stahding'il2 hoursiwhite crystalsseparatedwhich we're filtered-"ofi and reacrystallized, frornle'thyli acetate,-Z M; .P.i135" 136. 5 -Additional recrys'tallizations raised the melting fipoint slowly to l48' 150.- However','recr-ys'tallizatio nfromwvatergaveveryjwell formed. crys'tals -l'nel ting at .iss-ise iwhich' .were "evidently hyer ed .A-Yi iti m;

Calculated Found 0 m '71. s 171. s

aHa

Six grams of (0.02 mole) of 2-ditnethylamino- 4,4-diphenyl-5-hexanol was dissolved in 50 ml. of dry benzene. To this solution was added 6 gm. (excess) of phenylacetyl chloride. The resulting mixture became warm spontaneously and was refluxed one hour to complete the reaction. The benzene was distilled off and 50 ml. of ether added. On standing in the cold room with casional scratching crystals slowly formed in the oily lower layer. These were filtered off and recrystallized from ethyl acetate; the material melted at 170-172. A second recrystallization from the same solvent gave 5.7 gm. of crystals melting at 172-173.

Calculated for C29H35NO2-HC12 Calculated Found Example 7 The preparation of 2-dimethylamino-4,4-diphenyl--propionoxyheptane hydrochloride having the formula:

Six grams (0.02 mole) of crystalline 2-dimethylamino-4,1-diphenyl-5-heptanol was dissolved in 50 ml. of dry benzene and refluxed for 2 hours with 3.7 gm. (0.04 mole) or propionyl chloride. In 30 minutes after heating was begun the flask was filled with a crystalline precipitate. The reaction mixture was cooled and the crystals filtered off. This material melted at 185186 after recrystallization from isopropanol. It was found the material melted and resolidified when immersed in a melting point bath pre-heated to 150. This indicated the product was solvated. Yield 5 gm.

Calculated for C24H33NO2-HC1, mol. Wt. 403.73 (dried sample) Calculated Found Ten grams (0.03 mole) of amidone hydrochloride was reduced according to the method of Example 1. The ether extract of the alcohol obtained through that procedure was dried over potassium carbonate and filtered. To the solu- 6 tion was added 5 gm. (excess) of phenylisocyanate. Some light colored crystals separated in 12 hours which melted, after recrystallization from ethyl alcohol, at 238-239. Through a mixed melting point determination with an authenic sample, this product was shown to be diphenylurea. The supernatant ether layer above the crystals was extracted with 4 normal hydrochloric acid (300 m1.). These extracts on standing in the cold deposited needle crystals. These melted at 148-150". A second recrystallization from equal parts of methanol and hydrochloric acid gave crystals melting at 150l51 to a turbid liquid which slowly became clear at that temperature. Analysis showed this behavior due to the existence of the compound as a hydrate.

Calculated for C1sI-I34N2Oz.I-I2O.HC1, mol. wt. 484.74:

Calculated Found Example 9 The preparation of Z-dimethyIaminQ- lA-diphenyl-5- (alpha-chloroacetoxy) -heptane hydrochloride having the formulai Calculated Found Example 10 The preparation of ethyl-(2-dimethylamino- 4,4-diphenyl-5-heptyl) carbonate hydrochloride having the formula:

H T /CH3 CHa--CHz-C(l3CH2CHN H01 a CH3 A solution of 4 gm. (0.013 mole) of 2-dimethylamino-4,4-diphenyl-5heptanol in 50 ml. of ethyl acetate was refluxed for two hours with 3 gm. (0.028 mole) of ethyl chlorocarbonate. A portion of the solution crystallized when diluted with Skellysolve C. The original reaction mixture crystallized from ethylacetate; Four grams of white crystals melting at 16.7169 was obtained.

Calculated for C24H33N03.HC1

Calculated l Found C 68'. 70 68. 70 I 8. l7 8. 18

Example 11 In 75 ml.- of'water wascdissolvedsix grams of des-methyl amidone -l=dimethylamino-3,3=diphenyll-hexanone) To the solution was added 0.5 gram of Adams platinum oxide catalyst. The compound was then hydrogenated in a'Burgess- Parr reduction apparatus with an initial hydrogen pressure of '55 pounds. 'No hydrogen absorption was noted afterthefirst hour-although a three hour reaction period was allowed. The catalyst was removed by filtration and the filtrate made basic with 20% ."sodium hydroxide. The oil which separated'was extracted with 500 m1. of diethyl ether in three. portions. The-"extracts were dried over potassium ca'r bonate and converted to the nitrate salt through'the addition of concentratedacid with shaking'to the ether solution filtered from the ldrying. agent. .The oil which separated was allowed .to settle and the ether decanted. The oil was dissolved in hot isopropanol and the solution cooled. Plate crystals separated which were filtered-off and twice more recrystallized from thesamesolvent. The product was en meltedat 156-l57..

-Calculated fOr--C20H27NO.HNO32 I Example 12 The preparation of2=dimethylamino-4-phenyl- 4-cyclohexyl-5-heptano1 having the. formula:

and corresponding phosphatesalt.

Ten grams (0.029 mole) of amidone hydrochloride was dissolved in 80 ml. of glacial acetic acid and 1 gram of platinum oxidecatalyst added. This mixture was-shaken -on.a Burgess'eParr reduction apparatus at 50-60" with aniinitialilhydrogen pressure of 55 pounds. Over a three day period a pressure drop of 12.5 pounds was observed. Complete reduction of :bothvbenzene rings and the carbonyl group would require a pressure drop of 1716 pounds on the particular apparatus used. At this stage further addition of catalyst caused no additional uptake of hydrogen. The catalyst was then filtered oil and the filtrate concentrated to one third its original vvolinne. vThe solutiomwas then" made-Ibasic and the oil takensu p inether. The 'onlysaltobtainable in solidformwas a phosphate. Repeated reorystallizationof .the material did not give material with a. sharpmelting point.

The ether: solution. of the. base was then concentrated-and the residual oil vacuumdistilled.

8 After a forerun to 150, a fraction boiling at l50--1 53;:at pressure was collected. The oil obtained was analyzed. Calculatedon the basisv of one-benzene ring being reduced in addition to thecarbonyl group the: compound would have the following empirical formula and analy- Calculated for C21H35NO:

Calculated Calculated Found C 78. 2 79. H i. 12. 78 ll. 10

Example 13 The preparation of l-morpholino-3,3-diphenyll-hexanol having the following formula:

A solution of 10 grams (0.028 mole) of l-morpholino-3.3-diphenyl-4-hexanone hydrochloride in ml. of distilled water was placed in a reduction bottle with-0.2 grams of Adams platinum oxide'catalyst. The compound was hydrogenated in a Burgess-Parr apparatus with an initial hydrogen pressure of 55 pounds. In approximately 3 hours'less than 50% of the theoretical pressure drop for complete reduction of the carbonyl group had occurred. The spent catalyst was filtered 0i? and 012 gram of fresh platinum oxide catalyst added. on rehydrogenation the theoretical pressure drop was observed in one hour. The catalyst was then filtered offend the filtrate made basic with 40% sodium hydroxide solution. The heavy oil which separated'was extracted with ether and the ether extracts dried over potassium carbonate. Of various salts investigated only the nitrate could be crystallized. However, a portion of the ether solution was evaporated to dryness and the oil resulting crystallized. Recrystallization of the base fromcyclohexane gave material melting at 128-131. Another recrystallization from the same solvent gave large crystals melting at 130-131".

Calculated for C22H29NO22 Calculated Found C 77. 80 77. 7 H 8.63 S. 89

9 Calculated for caramel-"envoy Calculated Found Example '14 The preparation of 2-morpholino-4,4-diphenyl- 5-heptanol having the formula:

Calculated Ten grams (0.025 mole) of 2-morpholino-4,4- diphenyl-5-heptanone hydrochloride was dissolved in 150 ml. of distilled water. The solution was placed on the Parr reduction apparatus after addition of 0.30 gm. of Adams platinum oxide catalyst (American Platinum Works). A drop in hydrogen pressure corresponding to the theoretical amount needed for reduction of the carbonyl group was observed in two hours. The catalyst was filtered olf and the filtrate made basic. The oil soon crystallized and was recrystallized from methanol. The yield obtained through combining the first crop of crystals with a second crop resulting after concentration of the 5-acetoxy-heptane hydrochloride having the formula:

' methyl mother liquor was 8.5 gm. or 96%. The crystals melted at 118-119".

Calculated for CZSIBINOZI Calculated Found 0 .J. 7s. 30 7s. 10 H- 8.85 s. 83

The base dissolved in 300 ml. of dry ether and was saturated with dry hydrogen chloride. The white precipitate was filtered off and recrystallized from 700 ml. of anhydrous ethyl acetate. The long rectilinear crystals were filtered OE and the mother liquors concentrated to 200 ml. Both crops of crystals melted at 225-226. The yield was 9 gm. or 92.7% of theory on the basis of ketone starting material.

Example 15 The preparation of 2-morpho1ino 4A- diphenyl- O-HCl GET-CHI A solution of 5 gm. (0.014 mole) of 2-morpholino-4,4-diphenyl-5-heptanol in 50 ml. of dry benzene was treated with 5 gm. (excess) of acetyl chloride. The mixture was refluxed for one and one half hours and was then cooled. Crystals separated which after recrystallization from isobutyl ketone melted at 221-222". Yield 3 gm.

Calculated for CzaIhsNOzrHCl:

Calculated Found 0 e9. 46 69. 50 H 7. 94 s. 22

The preparation of 2-morpholino-4,4di-

Calculated Found Example 16 The preparation of alpha, alpha, diphenylgamma morpholino valeronitrile and alpha, alpha-diphenyl beta methyl-gamma-morpholinobutyronitrile.

3 \H ore-on. 3m

CHPCH2 CH-OHz-N 0 a CH3 CH2C a A mixture of 41.4 gm. (1.8 mole) of lithium amide, 289 gm. (1.5 mole) of diphenylacetonitrile and .500 ml. of anhydrous benzene was refluxed in all glass apparatus for 16 hours. To this mix.- ture was added a solution of beta-morpholinopropyl chloride prepared from 318 gm. (1.6 mole) of beta-morpholinopropyl chloride hydrochloride.

. 3' (Prepared according to the method describedin Oifice of the Publication Board, Department of Commerce, -Washington,- D. C., report.number PB-981 (page 96, No; 1) dated July 1945, with morpholine substituted for dimethylamine.) 5 The halide was added in solution in 500 ml. of benzene. The mixture was refluxed for eight hours and then cooled. Ice was added .to.the mixture with stirring. The two 'layerswere'them transferred toaseparatory funnel and'-shaken"l0 well: The benzene'layer was further washed with" 1 two 200ml; portionspfwater; After dryingover' potassiiun carbonate the benzene solution was concentratedandlast'traces of solvent removed under reducedpressure; The residue becamelfi partly crystalline onstanding. Yield: 479 gm.', 90.4%. A portion 'of-*the'materialwas pressed on filter. paper to remove oil and was .then recrystallized from ethyl alcohol. The crystals obtained melted from 99.102.. A secondrecrystaL. lization did not alter this value.

Calculated for C21H24N2O Example 17 The preparation of 2-morpholino4,4-diphenyl 5 heptanone, 1-morpholino 3,3 diphenyl-2-methyl-4-hexanone and related derivatives. A solution of 320 gm. (1 mole) of the' isomeric nitriles; alpha, alpha-diphenyl-.gamma,-. morpholino-valeronitrile, and alpha, alpha-di- O phenyl beta methyl-gamma-morpholinobutyronitrile, in 400 ml. of dry'xylenewas added to-a solution of ethyl magnesium bromide. -The .eth-ylmagnesium bromide. solution was prepared -from 48 gm. (2 mole) of magnesium metal and 2.18 gm; 1. (2 mole) of ethyl bromide with 500 ml. of dry ether as a solvent. All operations were carried out in a dry nitrogen atmosphere. After the addition of the Grignardweagent to the.nitri-le;-' the mixtureiwas refiuxed for sixhours. The greenish reaction mixture.was-.-then poured-as-50 rapidly as possible into a 4-liter beaker containing l-liter of water and 500 ml. of concentrated" hydrochloric acid. An exceedingly vigorous reaction followed. When the mixture had cooled somewhat 500 ml. of benzene was added and after stirring, three layers separated. In a few hours the heavy red middle layer sank to the bottom and began to crystallize. After 48 hours the mixture was filtered and ressed as dry as possible. The brown solid remaining-in the funnel was washed with ether, air dried to remove the solvent and then recrystallized from 1500 ml. of water. The yield of crystals obtained was 235 gm. (theoretical yield of oneisomer 216.1 gm.). The .material was then recrystallized from isopropanol in two portions. Thetotal volume of solvent used was.2,440 ml. The yield of crystals obtained was 1.71 gnnwhichwas 79.3% of theory: The filtrates from'both water and isopropanol' recrystallizations'were investigated for the other isomer expected in the reaction. Howevery'thi's first" fraction of producttfobtained melted. at" 230-231 and further. recrystallizations'" from. t

-.;Wat er or isopropanol did not alter the value. "As 7 he resulting compound was shown by analysis to 7 12:51: be a ketone, it was assigned the following structure.

47H: dfHrCz Calculated for C23Hz9N02 HBr Calculated Found ml. "of 4 normahliydrochlorio..acid...and the extracts addd to ther-facidslayer Fofv vvthe filtrate.- The combined acidsolutions were made basic and extracted-withbenzener 'Iheextracts, about one zliter. in.-.volume, were dried over potassium carbonatev-and concentratedr Theheavy oil which: remained recrystallized. .well .from. Skellysolve C. The"rectilinearcrystals obtained melted at 104- 105? "As the'product'reacted'rapidly with uct-was assignedaitlie':iiollowingzstructure..

(B). CalcnlatedtdomCnHsbNm a Calculated Found The filtrate from the water recrystallization of the"product"assigned"structureflm was made basic 'andfa; heavy oil separated. This oil was taken-'up-in 'boilingzethanoland cooledf Crystals crystallization frorn' SkellysolveC they melted sharply "at 139 140".""Tli yield obtained was 35 of the imineaassigned; to (structure? (B) .thata basawas-obtained meltingat 15395140 2? Thebase melted'i-undepressedrati-m9 9140% whenimixedvwith a samplewof athermaterial-aobtaineddrom the. re- 4 crystallization mother liquorswlIhus the product was vassigned thez-t-fiollowing Structure (C) Calculatedrior-.GzsI-IzsNOza.

CH CH:

0 orb-"o Example 18 The preparation of 2-morpholino-4,4diphenyl- -chloroacetoxyheptane hydrochloride having the formula:

Calculated Found Example 19 The preparation of the carbinol of isoamidone, having the formula:

A solution of 23 gm. (0.06 mole) of l-dimethylamino-2-methyl-3,3 diphenyl 4 hexylidineimine dihydrochloride was prepared in 200 ml. of concentrated hydrochloric acid and 50 ml. of water. This solution was refluxed for 48 hours to yield a solution of the corresponding ketone hydrochloride. The free base was liberated through addition of concentrated sodium hydroxide. The base was extracted into 800 ml. of ether. The solution of l-dimethylamino-Z- methyl-3,3-diphenyl-4-hexanone was dried over potassium carbonate and was then shaken for 2 hours with potassium hydroxide pellets. The dried solution was then added dropwise to a solution of 2.5 gm. (0.067 mole) of lithium aluminum hydride in 300 ml. of anhydrous ethyl ether. The reaction was moderately exothermic and the solvent boiled gently. After the addition the mixture was refluxed for 18 hours and was then cooled. Ice-water was added dropwise until no further evolution of hydrogen was noted. The mixture was then poured into a separatory funnel and 200 ml. of 20% sodium hydroxide added. The ether layer was separated and later combined with 500 m1. of ether used to extract the water layer in three portions. The combined ether solutions were dried over potassium carbonate, filtered and saturated with dry hydrogen chloride. The oily material which separated crystallized on boiling with anhydrous ethyl acetate. The product crystallized as long hairlike needles which melted at 203-204 to an oil which immediately crystallized. again melted at 236-237".

The material was submitted for analysis.

Calculated for C21H29NO-HC1f Calculated The material 14 The free base was isolated as crystals from Skellysolve C melting at l08l10.

Calculated for C21H29NO:

Calculated Found Example 20 The preparation of the acetate of isoamidol having the formula:

Five gm. (0.016 mole) of 1-dimethylamino-2- methyl-3,3-diphenyl 4 hexanol hydrochloride was dissolved in water and excess of 20% sodium hydroxide added. The dry base was isolated through extraction with ether, drying over potassium carbonatev and concentration of the ether solution. The oil remaining was dissolved in 50 ml. of ethyl acetate and 3 gm. (0.038 mole) of acetyl chloride added. The mixture was refluxed for two hours and cooled. The crystals which slowly separated were filtered off after 24 hours. Five gm. of product melting at 228-229 was obtained.

Calculated for C23H31NO2-HC12 In addition to the compounds described above other organic carbinols and esters thereof are included within the scope of this invention which can be prepared according to the above methods are:

2 dimethylamino 4,4 diphenyl 5 chloroacetoxy hexane hydrochloride, l-dimethylamino- Z-methyl 3,3 diphenyl 4 chloroacetoxypentane hydrochloride, Z-dimethylamino 4,4 diphenyl-5- (beta-chloropropionoxy) -heptane hydrochloride, 2-dimethylamino-4,4 diphenyl 5- (alpha-chloropropionoxy)-heptane hydrochloride, 2-dimethylamino-4,4-diphenyl-5-dichloroacetoxy heptane hydrochloride, Z-dimethylamino- 4,4-diphenyl-5-trichloroacetoxy heptane hydrochloride, 2-dimethy1amino-4,4-diphenyl-5-iodoacetoxy heptane hydrochloride, 2-dimethylamino-4,4-diphenyl-5-dibromoacetoxy heptane hydrochloride, 2-dimethylamino-4,4-diphenyl-5- methoxyheptane hydrochloride, 2dimethylamino-4,4-diphenyl-5-ethoxyheptane hydrochloride, 2-dimethylamino 4,4 diphenyl 5 (betachloroethoxy) heptane hydrochloride, 2-(N- morpholinyl)-4,4-diphenyl-5-ethoxyheptane hydrochloride, 1- (N-morpholinyl) -4,4-diphenyl-5- ethoxyheptane hydrochloride, ethyl-2-(N-morpholinyl(-4,4-diphenyl-5-heptyl carbonate hydrochloride, beta-chloroethyl 2-(N-morpholinyl)-4,4-diphenyl-5-heptyl carbonate hydrochloride, beta-chloroethyl 1-N-morpholinyl-3,3-di

phenyl-l-hexyl carbonate. hydrochloride, betachloroethyl l dimethylamino 3f diphenyl-4- hexyl carbonate hydrochloride, N-ethyl 2-dimethylamino-4,4-diphenyl--heptyl hydrochloride, N-methyl 1-dimethylamino-2- methyl-3,3-diphenyl-4-hexyl carbamate. hydrochloride, 2-dimethylamino-4,4-diphenyl-5-heptyl carbamate hydrochloride, l-dimethylamino-2- methyl-3,3-diphenyl-4-hexyl carbamate hydrochloride, 1-(N-pyrrolidyl-2-methyl3,3-diphenyl- 4-acetoxy-hexane hydrochloride, 2-(N-pyrrolidyl)-4,4-diphenyl-5-acetoxyheptane hydrochloride, 2- (N-pyrrolidyl) -4,4-dipheny1-5-chloroacetoxyheptane hydrochloride, 2-(N-pyrrolidyl)-4,4- dipheny1-5-chloroacetoxyhexane hydrochloride, Z-(N-pyrrolidyl) 4,4 diphenyl 5 chloroacetoxyoctane hydrochloride, 3-(N-pyrrolidyl)-5,5- diphenyl 6 chloroacetoxyoctane hydrochloride, 3 dimethylamino-5,5-diphenyl-G-chloracetoxyoctane hydrochloride, 2 dimethylamino 3- methyl-4,4-diphenyl-5-acetoxyv :heptane hydrochloride, 2-dimethylamino-4,4-diphenyl-5-butyroxyheptane hydrochloride, 2-(N-piperidyD-4,4- diphenyl-5-chloroacetoxyheptane hydrochloride, l-(N-piperidyl) -2-methyl-3,3-diphenyl 4 acetoxy hexane hydrochloride, 2-(N-a1pha-picolyh- 4,4-diphenyl-5-chloroacetoxyheptane hydrochloride, 2- (N-beta-picolyl) +4,4diphenyl-5ch1oroacetoxyheptane hydrochloride, 2-(N-gammapicolyl) -4,4-diphenyl 5 chloroacetoxyheptane hydrochloride, 2-diethylamino 4,4 diphenyl-5- acetoxyheptane hydrochloride, Z-dipropylamino- 4,4-diphenyl-5-acetoxyheptane hydrochloride, 2- din-butylamino-4,4 diphenyl 5 acetoxyheptane hydrochloride, 2-di-isobutylamino4,4-diphenyl-5-acetoxyheptane hydrochloride, 1-dimethy1amino-4,4-diphenyl 5 acetoXyhepta-ne hydrochloride, 2-isopropylamino-4,4-diphenyl-5- acetoxyheptane hydrochloride, Z-dimethylamino-4-(para-chlorophenyl) 4 phenyl 5 acetoxyheptane hydrochloride, 1-dimethylamino -2- methyl-4-(para-chlorophenyl) 4 phenyl 5- acetoxyheptane hydrochloride, 2-(N-morpholinyl) -4-(para-chlorophenyl) -4 phenyl 5 acetoxyheptane hydrochloride, l-(N-morpholinyD- 4 (para chlorophenyl) 4 phenyl 5 acetoxyheptane hydrochloride, 2-(N-pyrrolidyl) -4- (para-chlorophenyl)-4-phenyl 5 acetoxyheptane hydrochloride, 2-dimethylamino-4,4-(dipara-chlorophenyl) 5 acetoxyheptane hydrochloride, 2 dimethylamino 4 (ortho chlorophenyl-4-phenyl 5 acetoxyheptane hydrochloride, 2dimethylamino-4,4-(di-orthochlorophenyl)-5-acetoxyheptane hydrochloride, 2-dimethylamino 4 (para bromophenyl) 4 (orthobromophenyl)-5-acetoxyheptane hydrochloride, l-dimethylamino-2-methyl 3 (para methoxyphenyl) -3-phenyl-4-acetoxyhexane hydrochloride, 2-dimethylamino-4,4-di-(meta-methoxyphenyl)-5-ch1oroacetoxyheptane hydrochloride, 2-dimethylamino-4,4-di (meta hydroxyphenyl)-5-chloroacetoxyheptane hydrochloride, 2- N-morpholinyl-4,4 di (meta-hydroxyphenyl) 5-chloroacetoxyheptane hydrochloride, 2 (N- pyrrolidyl) -4,4-di-(meta hydroxyphenyl) 5- chloroacetoxyheptane hydrochloride, 2-(N- pyrrolidyl) 4,4 di (orthotolyl) 5 acetoxyheptane hydrochloride, 2-dimethylamino-4,4-di- (para-tolyl) -5-bromoacetoxyheptane hydrochloride, 2-dimethylamino-4-benzyl 4 phenyl 5 acetoxyheptane hydrochloride, 2-dimethylamino-4,4-dibenzyl 5 acetoxyheptane hydrochloride, 1-dimethylamino-3,3-dicyclopentyl-5-acetcarb amate chloride,

3,3-diphenyl-4-acetoxynonane hydrochloride, 1-

16 dimethylamino-3-phenanthryl 3 phenyl 4- acetoxyhexane hydrochloride, I-dimethylamino- B-naphthyI-B-phenyl 4 acetoxyhexane hydro- 1-dimethylamino-3- (alpha pyridy1) 3-phenyl-4-acetoxyhexane hydrochloride, 2-dimethylamino 4,4 di-(alpha-pyridyl) 5 acetoxyheptane hydrochloride, 2 dimethylamino- 4-phenyl-4-(alpha-pyrimidyl) 5 acetoxyheptane hydrochloride, 2-dimethylamino-4,4-di-(alpha-pyrimidyl) 5 acetoxyheptane hydrochloride, 1 dimethylamino 3 phenyl 3 (alphathienyD-4-acetoxy hexane hydrochloride, 2-dimethylamino-4-phenyl 4 (alpha-thienyl) 5- acetoxy heptane hydrochloride, 2-dimethylamino-4-phenyl-4-(alpha-thienyl) 5 chloroacetoxyheptane hydrochloride, Z-(N-morpholinyD- 4-phenyl-4 (alpha-thienyl) 5 chloroacetoxy heptane hydrochloride, 2-dimethy1amino-4,4-di- (alpha-thienyl) -5-chloroacetoxy heptane hydrochloride, 2-dimethylamino 4,4 di (beta-thienyl) -5- chloroacetoxyheptane hydrochloride.

The above description and examples are intended to be illustrative only. Any modification of or variation therefrom which conforms to the spirit of the invention is intended to be included within the scope of the claims.

I claim:

1. A member selected from the group consisting of ((1) compounds having the formula wherein R is a member selected from the group consisting of methyl and hydrogen and B is a member selected from the group consisting of dimethylamino and morpholino and (b) acid addition salts thereof.

2. A compound having the formula 3. A compound having the formula 17 18 4. A compound having the formula References Cited in the file of this patent UNITED STATES PATENTS m001 Number Name Date I 2,368,073 Tyron Jan. 23, 1945 f 2,431,285 Suter et a1 Nov. 18, 1947 I 2,477,842 Wenner Aug. 2, 1949 10 Number Country Date 24,631 Great Britain of 1903 OTHER REFERENCES Richter-Text Book of Organic Chemistry, 1938 ed., John Wiley and Sons, Inc., New York, pp.

MERRILL E- SPEETER. 15 2 5 d 

1. A MEMBER SELECTED FROM THE GROUP CONSISTING OF (A) COMPOUNDS HAVING THE FORMULA 